Acute effects of morphine and chlorpromazine on the acquisition of shuttle box conditioned avoidance response

Morphine sulfate, 0.25-24.0 mg/kg, or chlorpromazine hydrochloride, 0.0625-4.0mg/kg were administered subcutaneously to naive rats 30 min prior to the start of massed-trials conditioned avoidance response (CAR) testing. The graded doses of both drugs were applied in each of three CAR task difficulty levels created by manipulation of the duration of conditioned and unconditioned stimuli, intertrial interval and shock intensity. Chlorpromazine, in a dose-related manner, caused a decrement in CAR acquisition in all tasks. Morphine, in comparison, produced a biphasic dose response. For a given task difficulty, low doses of morphine enhanced acquisition, whereas higher doses inhibited acquisition. With increasing task difficulty, relatively larger doses of morphine were required to inhibit or facilitate acquisition of CAR. These results emphasize the need to consider not only drug dosage levels, but also the interaction of task difficulty in the application of drugs in learning paradigms.